Cesium fluoride → 6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-methoxypyrimidine-4-carboxylic acid methyl ester

HRID 1969354노트

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HRID 1969354 반응식
[CH3:1][O:2][C:3]([C:5]1[C:10]([O:11][CH3:12])=[C:9]([NH2:13])[N:8]=[C:7](Cl)[N:6]=1)=[O:4].[Cl:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[C:18]([F:25])[C:17]=1[O:26][CH3:27].[F-].[Cs+]>COCCOC.O.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:10]([O:11][CH3:12])=[C:9]([NH2:13])[N:8]=[C:7]([C:19]2[CH:20]=[CH:21][C:16]([Cl:15])=[C:17]([O:26][CH3:27])[C:18]=2[F:25])[N:6]=1)=[O:4]

참가 물질

8

반응물 3

HCID 25953Cesium fluorideHCID 441297064-Chloro-2-fluoro-3-methoxyphenylboronic acidHCID 52270701Methyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate

생성물 1

HCID 591269286-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-methoxypyrimidine-4-carboxylic acid methyl ester수율 52.7%

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

6-Amino-2-chloro-5-methoxypyrimidine-4-carboxylic acid methyl ester (0.2 g, 0.9 mmol), 4-chloro-2-fluoro-3-methoxyphenylboronic acid (0.29 g, 1.4 mmol), bis(triphenylphosphine)palladium(II) dichloride (65 mg, 0.1 mmol), and cesium fluoride (0.28 g, 1.9 mmol) were combined in 1 mL of 1,2-dimethoxyethane and 1 mL of water. The reaction mixture was heated in a CEM microwave at 100° C. for 15 min (other temperature/time pairs used in the subsequent examples were 110° C. for 15 min and 150° C. for 5 min) The cooled reaction mixture was diluted with ethyl acetate, washed with water, washed with brine, dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) to yield the title compound (162 mg, 51.1% yield): mp 155-158° C.; 1H NMR (CDCl3): δ 7.58 (dd, 1H), 7.20 (dd, 1H), 5.56 (br s, 2H) 4.00 (s, 3H), 3.99 (d, 3H), 3.94 (s, 3H).

후처리

  1. custom) The cooled reaction mixture
  2. washwashed with water
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)

출처 및 근거

ORD 기록
ord-a9b6f38548ec4363950b300385e6b8d3
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426591B2

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